Trulicity ® (dulaglutid) injektion

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Trulicity® (dulaglutid): Användning hos patienter med nedsatt njurfunktion

Effekt och säkerhet liknade insulin glargin hos patienter med kronisk njursvikt. Användning rekommenderas ej vid njursjukdom i slutstadium.

Clinical Pharmacology Study

In a phase 1, PK study that evaluated a single dose of dulaglutide 1.5 mg in patients with renal impairment, including ESRD, no clinically relevant changes were noted in the PK parameters of dulaglutide.1

AWARD-7 Study

The AWARD-7 study was a randomized, multicenter, open-label (blinded for the dose of dulaglutide), 52-week study that compared the efficacy and safety of once-weekly dulaglutide 1.5 mg and once-weekly dulaglutide 0.75 mg with daily insulin glargine in the treatment of patients with T2DM and moderate-to-severe CKD.2

Results

All treatment groups demonstrated significant improvement in HbA1c from baseline to 26 and 52 weeks (p<.0001). The LSM change in HbA1c from baseline to 26 weeks was similar across treatment groups, thus demonstrating noninferiority of treatment with dulaglutide 1.5 mg and dulaglutide 0.75 mg compared with insulin glargine treatment (Table 1. Change in HbA1c From Baseline to 26 and 52 Weeks in Patients Treated With Dulaglutide 1.5 mg, Dulaglutide 0.75 mg, or Insulin Glargine).2

Table 1. Change in HbA1c From Baseline to 26 and 52 Weeks in Patients Treated With Dulaglutide 1.5 mg, Dulaglutide 0.75 mg, or Insulin Glargine2

HbA1c, %a

Dulaglutide 1.5 mg
(n=183)

Dulaglutide 0.75 mg
(n=180) 

Insulin Glargine
(n=186) 

Change from baseline to 26 weeks

-1.2 (0.1)b

-1.1 (0.1)b 

-1.1 (0.1)b

LSM difference (95% CI)

-0.05 (-0.26, 0.15)c

0.02 (-0.18, 0.22)d

N/A

Change from baseline to 52 weeks

-1.1 (0.1)b

-1.1 (0.1)b

-1.0 (0.1)b

LSM difference (95% CI)

-0.10 (-0.34, 0.14)c

-0.10 (-0.33, 0.13)e

N/A

Abbreviations: HbA1c = glycated hemoglobin; LSM = least squares mean; mITT = modified intention-to-treat; N/A = not applicable.

a Data presented as LSM (SE) unless otherwise indicated and based on mITT population, defined as all randomized patients who received ≥1 dose of treatment and who had ≥1 postrandomization HbA1c measurement.

b p<.0001 vs baseline.

c p<.0001 for noninferiority vs insulin glargine with a 0.4% margin; p<.05 for noninferiority vs insulin glargine with a 0.3% margin.

d p<.05 for noninferiority vs insulin glargine with a 0.4% margin.

e p<.0001 for noninferiority vs insulin glargine with a 0.4% margin.

Estimated Glomerular Filtration Rate

The LSM reduction in eGFR from baseline to 26 weeks was significantly smaller in the dulaglutide 1.5 mg and dulaglutide 0.75 mg treatment groups compared with the insulin glargine treatment group (p<.05). Likewise, the LSM reduction in eGFR from baseline to 52 weeks was less in the dulaglutide 1.5 mg and dulaglutide 0.75 mg treatment groups compared with the insulin glargine treatment group and reached significance when calculated based on cystatin C (p<.05) (Table 2. Change in eGFR From Baseline to 26 and 52 Weeks in Patients Treated With Dulaglutide 1.5 mg, Dulaglutide 0.75 mg, or Insulin Glargine).2

Table 2. Change in eGFR From Baseline to 26 and 52 Weeks in Patients Treated With Dulaglutide 1.5 mg, Dulaglutide 0.75 mg, or Insulin Glargine2

eGFR, mL/min/1.73m2a 

Dulaglutide 1.5 mg
(n=192)

Dulaglutide 0.75 mg
(n=190)

Insulin Glargine
(n=194)

CKD-EPI creatinine

Baseline, mean (SD)

38.1 (13.2)

38.3 (12.3)

38.5 (13.0)

Change from baseline to 26 weeks

-0.1 (-1.2, 1.0)b

-0.4 (-1.4, 0.7)b

-1.9 (-3.0, -0.9)c

Change from baseline to 52 weeks

-1.1 (-2.4, 0.2)

-1.5 (-2.8, -0.2)c

-2.9 (-4.2, -1.6)d

CKD-EPI cystatin C

Baseline, mean (SD)

37.3 (14.2)

37.7 (13.7)

38.3 (14.8)

Change from baseline to 26 weeks

0.8 (-0.7, 2.3)b

1.1 (-0.4, 2.5)e

-3.0 (-4.4, -1.5)d

Change from baseline to 52 weeks

-0.7 (-2.5, 1.0)b

-0.7 (-2.4, 1.1)b

-3.3 (-5.1, -1.6)c

Abbreviations: CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate; LSM = least squares mean.

a Data presented as LSM (95% CI) unless otherwise indicated and based on safety population, defined as all patients who received ≥1 dose of treatment and who had any postdose data.

b p<.05 vs insulin glargine.

c p<.05 vs baseline.

d p<.0001 vs baseline.

e p<.0001 vs insulin glargine.

Urine Albumin-to-Creatinine Ratio

In patients with baseline macroalbuminuria, there was a significant decrease in the LSM UACR from baseline to

  • 26 and 52 weeks in patients treated with dulaglutide 1.5 mg (26 weeks, p<.0001; 52 weeks, p=.0024), and

  • 26 weeks in patients treated with dulaglutide 0.75 mg (p=.0102).2

The decrease in the LSM UACR from baseline to 26 and 52 weeks was significantly greater in patients treated with dulaglutide 1.5 mg compared with those treated with insulin glargine (26 weeks, p=.0076; 52 weeks, p=.0205). The decrease was numerically greater in patients treated with dulaglutide 0.75 mg compared with those treated with insulin glargine.2

References

1. Loghin C, de la Peña A, Cui X, et al. Pharmacokinetics of once weekly dulaglutide in special populations [abstract]. Diabetes. 2014;63(suppl 1):A251. https://doi.org/10.2337/db14-833-1316

2. Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018;6(8):605-617. https://doi.org/10.1016/S2213-8587(18)30104-9

Glossary

AWARD = Assessment of Weekly AdministRation of LY2189265 in Diabetes

CKD = chronic kidney disease

eGFR = estimated glomerular filtration rate

ESRD = end-stage renal disease

HbA1c = glycated hemoglobin

LSM = least squares mean

PK = pharmacokinetic

T2DM = type 2 diabetes mellitus

UACR = urine albumin to creatinine ratio

Datum fӧr senaste ӧversyn 2018 M09 12


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